This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The focus of my research is the interaction between the alveolar epithelium and respiratory viral pathogens, specifically, the role of the alveolar epithelial cells in initiating an immune response in the lung. The model I am studying is rat coronavirus (RCoV) infection of primary cultures of rat alveolar type I and type II cells. Two strains of RCoV differ in tissue tropism and disease severity in the rat, yet they have both been isolated from the lung during natural infection. I have shown that both of these strains, Parker's RCoV (RCoV-P) and sialodacryoadenitis virus (SDAV), infect primary rat type I and type II cells. Furthermore, I have shown that RCoV infection of type I cells results in expression of CXC chemokines, which is dependent partly on the cytokine IL-1. The primary function of CXC chemokines is to recruit and activate neutrophils. Neutrophils are found early in tissues during coronavirus infection, however their role in viral clearance and/or immunopathology during coronavirus infection is not known. My goals are to 1) Identify pathways for neutrophil recruitment to the lung and activation upon RCoV infection;2) Determine the viral and host cell components that are required to initiate the IL-1 and CXC chemokine response;and 3) Examine the role of neutrophils in the outcome of disease, with regard to viral clearance and immunopathology. These studies will define the early events in the immune response upon viral infection of the lung and will lead to strategies for tipping the balance of the immune response toward viral clearance and away from immune-mediated pathology.